The deep biosphere is still the most understudied biome on our planet and our theoretical concepts and knowledge are mainly based off molecular analyses of recent years. However, molecular approaches alone can often not explain the complex interactions of microorganisms and of viruses and microbes in these ecosystems. Here, we introduce how coupling environmental genomics to microscopy methods can bolster our understanding of microbe-microbe and virus-host interactions of the deep biosphere. Using the example of Altiarchaeota, uncultivated and carbon-fixing archaea from the continental subsurface, the presented research covers aspects from biogeography over ultrastructure to viral infections. The results from our genome-informed microscopy cum metagenomics approach on viruses of Altiarchaeota do not only provide evidence for a previously unknown viral clade, they also challenge the current paradigm that lysogeny is the prominent lifestyle of viruses in the deep biosphere. We further used genome-informed microscopy to investigate the interaction of Altiarchaeota with other microorganisms and found corroborating evidence that Altiarchaeota employ specific defense mechanisms against an episymbiont, another archaeon. Although this symbiotic archaeon as well as the viruses can be seen as parasites of Altiarchaeota, we argue that the interactions have specific advantages for the host or for the accompanying microbial community of these subsurface ecosystems. The results presented herein provide examples for the complex microbe-microbe and virus-host interactions that are yet to be discovered in the active, deep biosphere of the continental subsurface.